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Ibrutinib and Rituximab for Steroid-Refractory or Dependent Chronic GVHD

Trial Status: Active

This phase I / II trial studies the safety and efficacy of ibrutinib and rituximab combination therapy in treating patients with chronic graft-versus-host-disease following allogeneic stem cell transplant. Based on the relative roles of inflammatory cytokines, T-cells and B-cells in the pathophysiology of chronic GVHD (cGVHD) and the favorable individual effects of ibrutinib and rituximab in the cGVHD setting, combination ibrutinib and rituximab may confer additive or potentially synergistic benefit in the management of this challenging process.

Inclusion Criteria

  • Recipients of an allogeneic bone marrow, cord blood or peripheral blood stem cell transplant. * (There will be no restrictions based upon underlying disease, donor source, degree of human leukocyte match [HLA] match, intensity of pre-transplant conditioning regimen or use of prior donor lymphocyte infusion[s].)
  • Chronic GVHD that is confirmed by clinical assessment and/or biopsy.
  • Either steroid-refractory or steroid-dependent chronic (c)GVHD.
  • Karnofsky performance status >= 60.

Exclusion Criteria

  • History of treatment with a tyrosine kinase inhibitor (eg, imatinib) or other moderate-to-significant CYPA4 inhibitor within 2 weeks of enrollment.
  • Renal insufficiency as follows: creatinine > 2.5 mg/dL or creatinine clearance (CrCl) < 30 ml/min.
  • Hepatic insufficiency as follows: serum bilirubin > 3 mg/dL or grade 3 or greater transaminitis at baseline (even if deemed due to GVHD) or cirrhosis (any Childs Pugh class).
  • History of cardiac dysrhythmias or known cardiovascular disease without formal cardiology clearance.
  • History of cerebro-vascular accident or intracranial hemorrhage within 6 months prior to enrollment.
  • History of non-intracranial hemorrhage and/or coagulopathy without formal coagulation clearance.
  • Uncontrolled infections not responsive to antibiotics, anti-viral medicines, or anti-fungal medicines; or infection requiring systemic treatment that was completed =< 14 days before enrollment.
  • History of other hematologic malignancy.
  • History of human immunodeficiency virus (HIV).
  • History of active hepatitis B virus (HBV) or hepatitis C virus (HCV) without formal infectious disease clearance.
  • Patients incapable of complying with routine follow up schedule or unable to be compliant with study therapy.
  • Active or within 3 months use of prohibited medications or substances (e.g., illicit drugs).

New Hampshire

Dartmouth Hitchcock Medical Center
Status: ACTIVE
Contact: John M. Hill
Phone: 603-650-4628


I. To assess the safety and tolerability of ibrutinib/rituximab combined therapy in patients with steroid dependent or refractory graft versus host disease (GVHD).


I. To assess the clinical efficacy of ibrutinib/rituximab combined therapy in patients with steroid dependent or refractory GVHD.

II. To determine relevant laboratory correlates underlying clinical response, or lack thereof.

OUTLINE: This is a phase I, dose-escalation study of ibrutinib followed by a phase II study.

Patients receive rituximab intravenously (IV) weekly for 4-8 weeks and ibrutinib PO once daily (QD). Treatment continuous in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Trial Phase Phase I/II

Trial Type Treatment

Lead Organization
Dartmouth Hitchcock Medical Center

Principal Investigator
John M. Hill

  • Primary ID D17120
  • Secondary IDs NCI-2019-04366, cphs 31218
  • ID NCT03689894